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Nat Immunol. 2016 Feb;17(2):122-31. doi: 10.1038/ni.3370.

Interleukin 33 is a guardian of barriers and a local alarmin.

Author information

Institute of Cellular Chemistry, Center for Biochemistry, Hannover Medical School, Hannover, Germany.
Immunology FB08, Justus-Liebig-University Giessen, Giessen, Germany.


Interleukin 33 (IL-33) is a member of the IL-1 family of cytokines with a growing number of target cells and a plethora of biological functions. Although it has commonalities with other IL-1 cytokines, IL-33 exhibits some unique features. Here we review the biology of IL-33 and its receptor and develop a working model that describes two 'lives' for IL-33-one intracellular and one extracellular. Under healthy conditions, constitutively produced, intracellular IL-33 participates in maintaining barrier function by regulating gene expression as a nuclear protein. In parallel, nuclear IL-33 functions as a stored alarmin that is released when barriers are breached. Extracellular IL-33 coordinates immune defense and repair mechanisms while also initiating differentiation of helper T cells as the adaptive immune response is triggered.

[Indexed for MEDLINE]

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